Metabolic regulation in normal and leukemic stem cells.

Cellular metabolism regulates oxidative and proteostatic stresses in hematopoietic stem cells (HSCs) during replication and aging. Metabolic adaptations drive the chemoresistance and immune evasion capacities of leukemic stem cells (LSCs) in disease initiation and recurrence. Metabolic adaptations and epigenetic mechanisms interact in LSCs. Metabolic changes impact both HSCs and LSCs through cell-intrinsic and -extrinsic mechanisms. Hematopoietic stem cells (HSCs) and leukemic stem cells (LSCs) are crucial for ensuring hematopoietic homeostasis and driving leukemia progression, respectively. Recent research has revealed that metabolic adaptations significantly regulate the function and survival of these stem cells. In this review, we provide an overview of how metabolic pathways regulate oxidative and proteostatic stresses in HSCs during homeostasis and aging. Furthermore, we highlight targetable metabolic pathways and explore their interactions with epigenetics and the microenvironment in addressing the chemoresistance and immune evasion capacities of LSCs. The metabolic differences between HSCs and LSCs have profound implications for therapeutic strategies. [ABSTRACT FROM AUTHOR]